Although the link between skeletal development in childhood and bone health later in life is increasingly well established, much remains to be learned about the determinants of bone development during childhood and how they contribute to risk of osteoporosis and bone fracture. This is, in part, because relatively few studies have longitudinally assessed bone development and mineral accretion in childhood. Even for well-known dietary factors such as fluoride, calcium, and vitamin D, no large cohort of children has been followed from birth through adolescence. The objective of our current proposal is to extend our ongoing longitudinal study into adolescence. Currently in its 5th year, our study is a broad investigation of the effects of key dietary factors, physical activity, candidate gene polymorphisms and parental information dual-energy X-ray absorptiometry (DXA), diet, physical activity and candidate genes) on important endpoints that include periodic DXA bone measures. Age 5 bone and physical activity assessments (n=470) were conducted and age 8 assessments are in progress (n=190 so far). Analyses thus far indicate age 5 bone measures are positively associated with height and weight, physical activity, COL1A2 and osteocalcin gene polymorphisms, fluoride, calcium and vitamin D. The overall objective of this renewal is to continue longitudinal assessment through the critical years of puberty. DXA analyses (including Hip Structural Analysis (HSA)) and peripheral quantitative computed tomography (pQCT) will be used to assess bone measures at ages 11 and 13. Dietary and physical activity questionnaire and accelerometry data will be collected, additional candidate gene analyses undertaken, and sexual maturation assessed. Bone measures will be analyzed cross-sectionally (ages 8, 11, and 13) and longitudinally (ages 5 to 13), and related to children's demographic, anthropometric, fluoride and other dietary, physical activity, sexual maturity, and genetic factors. An important focus will be statistical analysis of gene-environment interaction effects (e.g., calcium intake and vitamin D receptor genotype) and correlation with parental genotypes and bone measures. Continued study of this cohort with longitudinal dietary data collected from birth provides a unique opportunity to reveal major insights into the relative importance of modifiable and non-modifiable factors on bone development during childhood and adolescence, with implications for prevention of osteoporosis and bone fractures.